Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity

被引:24
作者
Schweizer, Leonille [1 ,2 ,3 ,4 ]
Thierfelder, Felix [1 ,2 ,3 ,4 ]
Thomas, Christian [5 ]
Soschinski, Patrick [5 ]
Suwala, Abigail [6 ,7 ]
Stichel, Damian [6 ,7 ]
Wefers, Annika K. [6 ,7 ,8 ]
Wessels, Lars [9 ]
Misch, Martin [9 ]
Kim, Hee-yeong [1 ,3 ,4 ]
Joedicke, Ruben [1 ,2 ,3 ]
Teichmann, Daniel [1 ,2 ,3 ]
Kaul, David [10 ]
Kahn, Johannes [11 ]
Bockmayr, Michael [2 ,3 ,12 ,13 ,14 ]
Hasselblatt, Martin [3 ]
Younsi, Alexander [15 ]
Unterberg, Andreas [15 ]
Knie, Bettina [16 ]
Walter, Jan [17 ]
Al Safatli, Diaa [17 ]
May, Sven-Axel [18 ]
Joedicke, Andreas [19 ]
Ntoulias, Georgios [19 ]
Moskopp, Dag [16 ]
Vajkoczy, Peter [9 ]
Heppner, Frank L. [1 ,2 ,3 ,22 ,23 ]
Capper, David [1 ,2 ,4 ]
Hartmann, Wolfgang [20 ]
Hartmann, Christian [21 ]
von Deimling, Andreas [6 ,7 ]
Reuss, David E. [6 ]
Schoeler, Anne [1 ,2 ,3 ,4 ]
Koch, Arend [1 ,2 ,3 ,4 ]
机构
[1] Charite Univ Med Berlin, Berlin Inst Hlth, Dept Neuropathol, Charitepl 1, D-10117 Berlin, Germany
[2] Free Univ Berlin, Charitepl 1, D-10117 Berlin, Germany
[3] Humboldt Univ, Charitepl 1, D-10117 Berlin, Germany
[4] German Canc Res Ctr, Partner Site Berlin, German Canc Consortium DKTK, Heidelberg, Germany
[5] Univ Hosp Munster, Inst Neuropathol, Pottkamp 2, Munster, Germany
[6] Heidelberg Univ Hosp, Inst Pathol, Dept Neuropathol, Heidelberg, Germany
[7] German Consortium Translat Canc Res DKTK, German Canc Res Ctr DKFZ, Clin Cooperat Unit Neuropathol, Heidelberg, Germany
[8] Hopp Childrens Canc Ctr KiTZ, Heidelberg, Germany
[9] Charite Univ Med Berlin, Dept Neurosurg, Berlin, Germany
[10] Charite Univ Med Berlin, Dept Radiat Oncol & Radiotherapy, Berlin, Germany
[11] Charite Univ Med Berlin, Dept Radiol, Berlin, Germany
[12] Charite Univ Med Berlin, Berlin Inst Hlth, Dept Pathol, Berlin, Germany
[13] Univ Med Ctr Hamburg Eppendorf, Dept Pediat Hematol & Oncol, Hamburg, Germany
[14] Childrens Canc Ctr Hamburg, Res Inst, Hamburg, Germany
[15] Heidelberg Univ Hosp, Dept Neurosurg, Heidelberg, Germany
[16] Vivantes Klinikum Friedrichshain, Dept Neurosurg, Berlin, Germany
[17] Univ Klinikum Jena, Dept Neurosurg, Jena, Germany
[18] Klinikum Chemnitz, Dept Neurosurg, Chemnitz, Germany
[19] Vivantes Klinikum Neukolln, Dept Neurosurg, Berlin, Germany
[20] Univ Hosp Munster, Gerhard Domagk Inst Pathol, Div Translat Pathol, Munster, Germany
[21] Hannover Med Sch, Inst Pathol, Dept Neuropathol, Hannover, Germany
[22] NeuroCure, Cluster Excellence, Charitepl 1, D-10117 Berlin, Germany
[23] German Ctr Neurodegenerat Dis DZNE Berlin, D-10117 Berlin, Germany
关键词
Paraganglioma; Cauda equina; Head and neck; SDHB; GATA3; DNA methylation; METHYLATION-BASED CLASSIFICATION; PHEOCHROMOCYTOMA; EXPRESSION; MUTATIONS; GATA3; HEAD;
D O I
10.1007/s00401-020-02218-7
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Paragangliomas/pheochromocytomas are rare neuroendocrine tumors that arise from the adrenal gland or ganglia at various sites throughout the body. They display a remarkable diversity of driver alterations and are associated with germline mutations in up to 40% of the cases. Comprehensive molecular profiling of abdomino-thoracic paragangliomas revealed four molecularly defined and clinically relevant subtypes. Paragangliomas of the cauda equina region are considered to belong to one of the defined molecular subtypes, but a systematic molecular analysis has not yet been performed. In this study, we analyzed genome-wide DNA methylation profiles of 57 cauda equina paragangliomas and show that these tumors are epigenetically distinct from non-spinal paragangliomas and other tumors. In contrast to paragangliomas of other sites, chromosomal imbalances are widely lacking in cauda equina paragangliomas. Furthermore, RNA and DNA exome sequencing revealed that frequent genetic alterations found in non-spinal paragangliomas-including the prognostically relevant SDH mutations-are absent in cauda equina paragangliomas. Histologically, cauda equina paragangliomas show frequently gangliocytic differentiation and strong immunoreactivity to pan-cytokeratin and cytokeratin 18, which is not common in paragangliomas of other sites. None of our cases had a familial paraganglioma syndrome. Tumors rarely recurred (9%) or presented with multiple lesions within the spinal compartment (7%), but did not metastasize outside the CNS. In summary, we show that cauda equina paragangliomas represent a distinct, sporadic tumor entity defined by a unique clinical and morpho-molecular profile.
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收藏
页码:893 / 906
页数:14
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